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1.
Int J Nanomedicine ; 19: 6427-6447, 2024.
Article in English | MEDLINE | ID: mdl-38952675

ABSTRACT

Background: Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals. Purpose: To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration. Methods: We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining. Results: Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects. Conclusion: NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.


Subject(s)
Anti-Bacterial Agents , Coated Materials, Biocompatible , Escherichia coli , Osteogenesis , Polylactic Acid-Polyglycolic Acid Copolymer , Rats, Sprague-Dawley , Staphylococcus aureus , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Osteogenesis/drug effects , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Mice , Staphylococcus aureus/drug effects , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Escherichia coli/drug effects , Cell Differentiation/drug effects , Prostheses and Implants , Alloys/pharmacology , Alloys/chemistry , Rats , Titanium/chemistry , Titanium/pharmacology , Silver/chemistry , Silver/pharmacology , Cell Proliferation/drug effects , Copper/chemistry , Copper/pharmacology , Male , X-Ray Microtomography , Cell Line , Metal Nanoparticles/chemistry
2.
Molecules ; 29(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38998976

ABSTRACT

AgCu bimetallic· nanoparticles (NPs) represent a novel class of inorganic, broad-spectrum antimicrobial agents that offer enhanced antimicrobial effectiveness and reduced cytotoxicity compared to conventional Ag NP antibacterial materials. This study examines the antimicrobial performance and structural characteristics of AgCu nanoparticles (NPs) synthesized via two distinct chemical reduction processes using PVP-PVA as stabilizers. Despite identical chemical elements and sphere-like shapes in both synthesis methods, the resulting AgCu nanoparticles exhibited significant differences in size and antimicrobial properties. Notably, AgCu NPs with smaller average particle sizes demonstrated weaker antimicrobial activity, as assessed by the minimum inhibitory concentration (MIC) measurement, contrary to conventional expectations. However, larger average particle-sized AgCu NPs showed superior antimicrobial effectiveness. High-resolution transmission electron microscopy analysis revealed that nearly all larger particle-sized nanoparticles were AgCu nanoalloys. In contrast, the smaller particle-sized samples consisted of both AgCu alloys and monometallic Ag and Cu NPs. The fraction of Ag ions (relative to the total silver amount) in the larger AgCu NPs was found to be around 9%, compared to only 5% in that of the smaller AgCu NPs. This indicates that the AgCu alloy content significantly contributes to enhanced antibacterial efficacy, as a higher AgCu content results in the increased release of Ag ions. These findings suggest that the enhanced antimicrobial efficacy of AgCu NPs is primarily attributed to their chemical composition and phase structures, rather than the size of the nanoparticles.


Subject(s)
Alloys , Copper , Metal Nanoparticles , Microbial Sensitivity Tests , Particle Size , Silver , Copper/chemistry , Metal Nanoparticles/chemistry , Alloys/chemistry , Alloys/pharmacology , Silver/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
3.
Chem Commun (Camb) ; 60(60): 7729-7732, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38973292

ABSTRACT

Implant infections are a major challenge for the healthcare system. Biofilm formation and increasing antibiotic resistance of common bacteria cause implant infections, leading to an urgent need for alternative antibacterial agents. In this study, the antibiofilm behaviour of a coating consisting of a silver (Ag)/gold (Au) nanoalloy is investigated. This alloy is crucial to reduce uncontrolled potentially toxic Ag+ ion release. In neutral pH environments this release is minimal, but the Ag+ ion release increases in acidic microenvironments caused by bacterial biofilms. We perform a detailed physicochemical characterization of the nanoalloys and compare their Ag+ ion release with that of pure Ag nanoparticles. Despite a lower released Ag+ ion concentration at pH 7.4, the antibiofilm activity against Escherichia coli (a bacterium known to produce acidic pH environments) is comparable to a pure nanosilver sample with a similar Ag-content. Finally, biocompatibility studies with mouse pre-osteoblasts reveal a decreased cytotoxicity for the alloy coatings and nanoparticles.


Subject(s)
Alloys , Anti-Bacterial Agents , Biofilms , Escherichia coli , Gold , Metal Nanoparticles , Silver , Silver/chemistry , Silver/pharmacology , Biofilms/drug effects , Gold/chemistry , Gold/pharmacology , Hydrogen-Ion Concentration , Mice , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Alloys/chemistry , Alloys/pharmacology , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Ions/chemistry , Ions/pharmacology , Prostheses and Implants , Cell Survival/drug effects
4.
ACS Appl Bio Mater ; 7(6): 3900-3914, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38840339

ABSTRACT

The poor clinical performance of titanium and its alloy implants is mainly attributed to their lack of antibacterial ability and poor osseointegration. The key and challenge lie in how to enhance their osteoinductivity while imparting antibacterial capability. In this study, a titanium oxide metasurface with light-responsive behavior was constructed on the surface of titanium alloy using an alkaline-acid bidirectional hydrothermal method. The effects of the acid type, acid concentration, hydrothermal time, hydrothermal temperature, and subsequent heat treatments on the optical behavior of the metasurface were systematically investigated with a focus on exploring the influence of the metasurface and photodynamic reaction on the osteogenic activity of osteoblasts. Results show that the type of acid and heat treatment significantly affect the light absorption of the titanium alloy surface, with HCl and post-heat-treatment favoring redshift in the light absorption. Under 808 nm near-infrared (NIR) irradiation for 10 min, in vitro antibacterial experiments demonstrate that the antibacterial rate of the metasurface titanium alloy against Staphylococcus aureus and Escherichia coli were 96.87% and 99.27%, respectively. In vitro cell experiments demonstrate that the nanostructure facilitates cell adhesion, proliferation, differentiation, and expression of osteogenic-related genes. Surprisingly, the nanostructure promoted the expression of relevant osteogenic genes of MC3T3-E1 under 808 nm NIR irradiation. This study provides a method for the surface modification of titanium alloy implants.


Subject(s)
Alloys , Anti-Bacterial Agents , Biocompatible Materials , Escherichia coli , Infrared Rays , Materials Testing , Nanostructures , Staphylococcus aureus , Surface Properties , Titanium , Titanium/chemistry , Titanium/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Staphylococcus aureus/drug effects , Alloys/chemistry , Alloys/pharmacology , Escherichia coli/drug effects , Nanostructures/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Microbial Sensitivity Tests , Particle Size , Animals , Mice , Osteogenesis/drug effects , Osteoblasts/drug effects , Osteoblasts/cytology , Cell Proliferation/drug effects , Osseointegration/drug effects
5.
ACS Appl Mater Interfaces ; 16(25): 31983-31996, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38865688

ABSTRACT

Effective osteointegration is of great importance for pedicle screws in spinal fusion surgeries. However, the lack of osteoinductive activity of current screws diminishes their feasibility for osteointegration and fixation, making screw loosening a common complication worldwide. In this study, Ti-6Al-4V pedicle screws with full through-hole design were fabricated via selective laser melting (SLM) 3D printing and then deposited with porous oxide coatings by microarc oxidation (MAO). The porous surface morphology of the oxide coating and the release of bioactive ions could effectively support cell adhesion, migration, vascularization, and osteogenesis in vitro. Furthermore, an in vivo goat model demonstrated the efficacy of modified screws in improving bone maturation and osseointegration, thus providing a promising method for feasible orthopedic internal fixation.


Subject(s)
Ceramics , Goats , Osseointegration , Oxidation-Reduction , Pedicle Screws , Printing, Three-Dimensional , Titanium , Animals , Osseointegration/drug effects , Titanium/chemistry , Titanium/pharmacology , Ceramics/chemistry , Ceramics/pharmacology , Alloys/chemistry , Alloys/pharmacology , Osteogenesis/drug effects , Humans , Porosity , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Cell Adhesion/drug effects
6.
ACS Appl Mater Interfaces ; 16(25): 32566-32577, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38867413

ABSTRACT

In this work, the hydroxyapatite (HA) microspheres are utilized as carriers for 8-hydroxyquinoline (8-HQ) inhibitors with a sodium alginate-silver nitrate layer (Ag-SA) added to confer chloride-responsive properties. These 8-HQ@Ag-SA-HA microspheres are subsequently integrated into poly(lactic acid) (PLA) coatings to produce biocompatible coatings. The resulting 8-HQ@Ag-SA-HA microsphere exhibits a spherical structure with a diameter of 3.16 µm. Thermogravimetric analysis indicates that the encapsulated 8-HQ inhibitors are approximately 11.83 wt %. Furthermore, the incorporation of these microspheres fills the micropores within the PLA coating, leading to a denser coating surface, enhanced wettability (contact angle value = 88°), and improved adhesion strength, thereby reinforcing the physical barrier effect. Corrosion tests reveal that the coatings exhibit increased resistance to corrosion in simulated body fluid (SBF) solutions. The released 8-HQ inhibitors in response to chloride ions form a protective layer of Mg(HQ)2, providing the coatings with self-healing properties and ensuring their durability in the SBF environment. Additionally, the cell test demonstrates a significant presence of MG-63 cells, accompanied by a low hemolysis rate of 3.81%, confirming the exceptional biocompatibility of the coatings. These findings offer valuable insights into the development of stimuli-responsive biocompatible coatings for effectively protecting Mg alloys.


Subject(s)
Alloys , Chlorides , Coated Materials, Biocompatible , Magnesium , Alloys/chemistry , Alloys/pharmacology , Humans , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Magnesium/chemistry , Magnesium/pharmacology , Chlorides/chemistry , Durapatite/chemistry , Durapatite/pharmacology , Corrosion , Microspheres , Alginates/chemistry , Polyesters/chemistry
7.
ACS Biomater Sci Eng ; 10(7): 4452-4462, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38875708

ABSTRACT

Mg-based biodegradable metallic implants are gaining increased attraction for applications in orthopedics and dentistry. However, their current applications are hampered by their high rate of corrosion, degradation, and rapid release of ions and gas bubbles into the physiological medium. The aim of the present study is to investigate the osteogenic and angiogenic potential of coated Mg-based implants in a sheep cranial defect model. Although their osteogenic potential was studied to some extent, their potential to regenerate vascularized bone formation was not studied in detail. We have studied the potential of magnesium-calcium (MgCa)-based alloys modified with zinc (Zn)- or gallium (Ga)-doped calcium phosphate (CaP) coatings as a strategy to control their degradation rate while enhancing bone regeneration capacity. MgCa and its implants with CaP coatings (MgCa/CaP) as undoped or as doped with Zn or Ga (MgCa/CaP + Zn and MgCa/CaP + Ga, respectively) were implanted in bone defects created in the sheep cranium. MgCa implants degraded faster than the others at 4 weeks postop and the weight loss was ca. 50%, while it was ca. 15% for MgCa/CaP and <10% in the presence of Zn and Ga with CaP coating. Scanning electron microscopy (SEM) analysis of the implant surfaces also revealed that the MgCa implants had the largest degree of structural breakdown of all the groups. Radiological evaluation revealed that surface modification with CaP to the MgCa implants induced better bone regeneration within the defects as well as the enhancement of bone-implant surface integration. Bone volume (%) within the defect was ca. 25% in the case of MgCa/CaP + Ga, while it was around 15% for undoped MgCa group upon micro-CT evaluation. This >1.5-fold increase in bone regeneration for MgCa/CaP + Ga implant was also observed in the histopathological examination of the H&E- and Masson's trichrome-stained sections. Immunohistochemical analysis of the bone regeneration (antiosteopontin) and neovascularization (anti-CD31) at the defect sites revealed >2-fold increase in the expression of the markers in both Ga- and Zn-doped, CaP-coated implants. Zn-doped implants further presented low inflammatory reaction, notable bone regeneration, and neovascularization among all the implant groups. These findings indicated that Ga- and Zn-doped CaP coating is an important strategy to control the degradation rate as well as to achieve enhanced bone regeneration capacity of the implants made of Mg-based alloys.


Subject(s)
Alloys , Calcium Phosphates , Coated Materials, Biocompatible , Gallium , Magnesium , Osteogenesis , Skull , Zinc , Animals , Zinc/chemistry , Zinc/pharmacology , Sheep , Skull/drug effects , Skull/pathology , Skull/injuries , Osteogenesis/drug effects , Magnesium/pharmacology , Gallium/chemistry , Gallium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Bone Regeneration/drug effects , Calcium/metabolism , Absorbable Implants
8.
Int J Biol Macromol ; 271(Pt 2): 132487, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38768910

ABSTRACT

Due to its biofunctions similar to NO, the CO gas signaling molecule has gradually shown great potential in cardiovascular biomaterials for regulating the in vivo performances after the implantation and has received increasing attention. To construct a bioactive surface with CO-releasing properties on the surface of magnesium-based alloy to augment the anticorrosion and biocompatibility, graphene oxide (GO) was firstly modified using carboxymethyl chitosan (CS), and then CO-releasing molecules (CORM401) were introduced to synthesize a novel biocompatible nanomaterial (GOCS-CO) that can release CO in the physiological environments. The GOCS-CO was further immobilized on the magnesium alloy surface modified by polydopamine coating with Zn2+ (PDA/Zn) to create a bioactive surface capable of releasing CO in the physiological environment. The outcomes showed that the CO-releasing coating can not only significantly enhance the anticorrosion and abate the corrosion degradation rate of the magnesium alloy in a simulated physiological environment, but also endow it with good hydrophilicity and a certain ability to adsorb albumin selectively. Owing to the significant enhancement of anticorrosion and hydrophilicity, coupled with the bioactivity of GOCS, the modified sample not only showed excellent ability to prevent platelet adhesion and activation and reduce hemolysis rate but also can promote endothelial cell (EC) adhesion, proliferation as well as the expression of nitric oxide (NO) and vascular endothelial growth factor (VEGF). In the case of CO release, the hemocompatibility and EC growth behaviors were further significantly improved, suggesting that CO molecules released from the surface can significantly improve the hemocompatibility and EC growth. Consequently, the present study provides a novel surface modification method that can simultaneously augment the anticorrosion and biocompatibility of magnesium-based alloys, which will strongly promote the research and application of CO-releasing bioactive coatings for surface functionalization of cardiovascular biomaterials and devices.


Subject(s)
Alloys , Chitosan , Coated Materials, Biocompatible , Graphite , Magnesium , Graphite/chemistry , Chitosan/chemistry , Chitosan/analogs & derivatives , Chitosan/pharmacology , Magnesium/chemistry , Magnesium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Humans , Carbon Monoxide/chemistry , Carbon Monoxide/pharmacology , Stents , Hemolysis/drug effects , Platelet Adhesiveness/drug effects , Corrosion , Cell Adhesion/drug effects , Materials Testing , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Proliferation/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Animals , Endothelial Cells/drug effects
9.
Acta Biomater ; 181: 469-482, 2024 06.
Article in English | MEDLINE | ID: mdl-38723926

ABSTRACT

Medium-entropy alloys (MEAs) typically exhibit outstanding mechanical properties, but their high Young's modulus results in restricted clinical applications. Mismatched Young's modulus between implant materials and human bones can lead to "stress shielding" effects, leading to implant failure. In contrast, ß-Ti alloys demonstrate a lower Young's modulus compared to MEAs, albeit with lower strength. In the present study, based on the bimodal grain size distribution (BGSD) strategy, a series of high-performance TiZrNbTa/Ti composites are obtained by combining TiZrNbTa MEA powders with nano-scale grain sizes and commercially pure Ti (CP-Ti) powders with micro-scale grain sizes. Concurrently, Zr, Nb, and Ta that are ß-Ti stabilizer elements diffuse into Ti, inducing an isomorphous transformation in Ti from the high Young's modulus α-Ti phase to the low Young's modulus ß-Ti phase at room temperature, optimizing the mechanical biocompatibility. The TiZrNbTa/ß-Ti composite demonstrates a yield strength of 1490 ± 83 MPa, ductility of 20.7 % ± 2.9 %, and Young's modulus of 87.6 ± 1.6 GPa. Notably, the yield strength of the TiZrNbTa/ß-Ti composite surpasses that of sintered CP-Ti by 2.6-fold, and its ductility outperforms TiZrNbTa MEA by 2.3-fold. The Young's modulus of the TiZrNbTa/ß-Ti composite is reduced by 28 % and 36 % compared to sintered CP-Ti and TiZrNbTa MEA, respectively. Additionally, it demonstrates superior biocompatibility compared to CP-Ti plate, sintered CP-Ti, and TiZrNbTa MEA. With a good combination of mechanical properties and biocompatibility, the TiZrNbTa/ß-Ti composite exhibits significant potential for clinical applications as metallic biomaterials. STATEMENT OF SIGNIFICANCE: This work combines TiZrNbTa MEA with nano-grains and commercially pure Ti with micro-grains to fabricate a TiZrNbTa/ß-Ti composite with bimodal grain-size, which achieves a yield strength of 1490 ± 83 MPa and a ductility of 20.7 % ± 2.9 %. Adhering to the ISO 10993-5 standard, the TiZrNbTa/ß-Ti composite qualifies as a non-cytotoxic material, achieving a Class 0 cytotoxicity rating and demonstrating outstanding biocompatibility akin to commercially pure Ti. Drawing on element diffusion, Zr, Nb, and Ta serve not only as solvent atoms to achieve solid-solution strengthening but also as stabilizers for the transformation of the ß-Ti crystal structure. This work offers a novel avenue for designing advanced biomedical Ti alloys with elevated strength and plasticity alongside a reduced Young's modulus.


Subject(s)
Alloys , Biocompatible Materials , Materials Testing , Titanium , Titanium/chemistry , Titanium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Animals , Elastic Modulus , Humans , Niobium/chemistry , Niobium/pharmacology , Zirconium/chemistry , Zirconium/pharmacology , Phase Transition , Mice
10.
Acta Biomater ; 182: 139-155, 2024 07 01.
Article in English | MEDLINE | ID: mdl-38750914

ABSTRACT

Additively manufactured (AM) biodegradable zinc (Zn) alloys have recently emerged as promising porous bone-substituting materials, due to their moderate degradation rates, good biocompatibility, geometrically ordered microarchitectures, and bone-mimicking mechanical properties. While AM Zn alloy porous scaffolds mimicking the mechanical properties of trabecular bone have been previously reported, mimicking the mechanical properties of cortical bone remains a formidable challenge. To overcome this challenge, we developed the AM Zn-3Mg alloy. We used laser powder bed fusion to process Zn-3Mg and compared it with pure Zn. The AM Zn-3Mg alloy exhibited significantly refined grains and a unique microstructure with interlaced α-Zn/Mg2Zn11 phases. The compressive properties of the solid Zn-3Mg specimens greatly exceeded their tensile properties, with a compressive yield strength of up to 601 MPa and an ultimate strain of >60 %. We then designed and fabricated functionally graded porous structures with a solid core and achieved cortical bone-mimicking mechanical properties, including a compressive yield strength of >120 MPa and an elastic modulus of ≈20 GPa. The biodegradation rates of the Zn-3Mg specimens were lower than those of pure Zn and could be adjusted by tuning the AM process parameters. The Zn-3Mg specimens also exhibited improved biocompatibility as compared to pure Zn, including higher metabolic activity and enhanced osteogenic behavior of MC3T3 cells cultured with the extracts from the Zn-3Mg alloy specimens. Altogether, these results marked major progress in developing AM porous biodegradable metallic bone substitutes, which paved the way toward clinical adoption of Zn-based scaffolds for the treatment of load-bearing bony defects. STATEMENT OF SIGNIFICANCE: Our study presents a significant advancement in the realm of biodegradable metallic bone substitutes through the development of an additively manufactured Zn-3Mg alloy. This novel alloy showcases refined grains and a distinctive microstructure, enabling the fabrication of functionally graded porous structures with mechanical properties resembling cortical bone. The achieved compressive yield strength and elastic modulus signify a critical leap toward mimicking the mechanical behavior of load-bearing bone. Moreover, our findings reveal tunable biodegradation rates and enhanced biocompatibility compared to pure Zn, emphasizing the potential clinical utility of Zn-based scaffolds for treating load-bearing bony defects. This breakthrough opens doors for the wider adoption of zinc-based materials in regenerative orthopedics.


Subject(s)
Alloys , Cortical Bone , Zinc , Alloys/chemistry , Alloys/pharmacology , Zinc/chemistry , Zinc/pharmacology , Animals , Mice , Cortical Bone/drug effects , Porosity , Magnesium/chemistry , Magnesium/pharmacology , Materials Testing , Compressive Strength , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Absorbable Implants , Elastic Modulus , Cell Line
11.
J Mater Chem B ; 12(23): 5661-5677, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38747312

ABSTRACT

Magnesium alloy is currently regarded as the most favourable biodegradable metal; however, obstacles remain to be overcome in terms of managing its corrosion and ensuring its biocompatibility. In this study, a metal-organic complex comprising Ca ions incorporated in tannic acid (TA) was prepared and used to coat magnesium alloy by chemical conversion and dipping processes, followed by modification with stearic acid (SA). This metal-organic complex coating was demonstrated to be homogeneous and compact, and it significantly improved the electrochemical corrosion resistance and long-term degradation behaviour of the coated samples. Consequently, the well-controlled release of Mg and Ca ions, as well as the osteo-compatible TA and SA molecules, promoted the proliferation of osteoblast cells. This metal-organic complex coating offers a promising modifying strategy for magnesium-based orthopaedic implants.


Subject(s)
Alloys , Coated Materials, Biocompatible , Magnesium , Magnesium/chemistry , Alloys/chemistry , Alloys/pharmacology , Corrosion , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Materials Testing , Tannins/chemistry , Tannins/pharmacology , Cell Proliferation/drug effects , Surface Properties , Osteoblasts/drug effects , Osteoblasts/cytology , Absorbable Implants , Humans , Stearic Acids/chemistry , Animals , Calcium/chemistry , Calcium/metabolism , Cell Line
12.
Colloids Surf B Biointerfaces ; 240: 113972, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38810469

ABSTRACT

Magnesium (Mg) and its alloys were favored by biomedical practitioners thanks to availability of bioactivity and degradability. However, the mismatch between the degradation properties of Mg alloys and the rate of osteogenesis often led to implant failure and bacterial infections within the desired period. The goal of this study was to improve the corrosion resistance of Mg alloys, providing theoretical guidance for solving the problems of implantable Mg-based materials. In this experiment, we prepared a dense and uniform BTESPT/TiO2 film layer on the surface of Mg substrate by electrochemically assisted deposition. The BTESPT/TiO2 film layer provided a physical barrier to avoid direct contact between AZ31 and the corrosive medium. When the addition amount was 2 g/L TiO2, the coating had the best corrosion resistance behavior, its corrosion current density could be up to 9.973×10-8 A/cm2. The BTESPT/TiO2 revealed good cell viability as well as osteogenic differentiation potential on MC3T3-E1 cells.


Subject(s)
Alloys , Electrochemical Techniques , Magnesium , Titanium , Titanium/chemistry , Titanium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Mice , Animals , Magnesium/chemistry , Corrosion , Surface Properties , Osteogenesis/drug effects , Cell Survival/drug effects , Cell Differentiation/drug effects , Sulfides/chemistry , Cell Line , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology
13.
Int J Biol Macromol ; 272(Pt 2): 132747, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38821301

ABSTRACT

Degradable magnesium alloy stents are considered to be ideal candidates to replace the traditional non-degradable stents for the treatment of cardiovascular diseases. However, bare magnesium alloy stents usually degrade too fast and show poor hemocompatibility and cytocompatibility, which seriously affects their clinical use. In this study, surface modification based on the MgF2 layer, polydopamine (PDA) coating, fucoidan and CAG peptides was performed on the Mg-Zn-Y-Nd (ZE21B) magnesium alloy with the purpose of improving its corrosion resistance, hemocompatibility and cytocompatibility for vascular stent application. After modification, the ZE21B alloy showed better corrosion resistance. Moreover, the lower hemolysis rate, platelet adhesion and activation, and fibrinogen adsorption and denaturation proved the improved hemocompatibility of modified ZE21B alloy in in vitro blood experiments. Furthermore, the co-immobilization of fucoidan and CAG peptides significantly promoted the adhesion, proliferation, migration and NO release of endothelial cells (ECs) on the modified ZE21B alloy, and meanwhile the modification with fucoidan and CAG peptides inhibited the adhesion and proliferation of smooth muscle cells (SMCs) and suppressed the expression of proinflammatory factors in the macrophages (MAs). The surface modification obviously enhanced the corrosion resistance, hemocompatibility and cytocompatibility of ZE21B alloy, and provided an effective strategy for the development of degradable vascular stents.


Subject(s)
Alloys , Cell Adhesion , Magnesium , Materials Testing , Peptides , Polysaccharides , Alloys/chemistry , Alloys/pharmacology , Polysaccharides/chemistry , Polysaccharides/pharmacology , Humans , Peptides/chemistry , Peptides/pharmacology , Magnesium/chemistry , Cell Adhesion/drug effects , Animals , Cell Proliferation/drug effects , Hemolysis/drug effects , Corrosion , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Platelet Adhesiveness/drug effects , Mice , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Surface Properties , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Aquatic Organisms/chemistry , Indoles , Polymers
14.
Adv Mater ; 36(29): e2401361, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38721975

ABSTRACT

Senescence plays a critical role in the development and progression of various diseases. This study introduces an amorphous, high-entropy alloy (HEA)-based nanozyme designed to combat senescence. By adjusting the nanozyme's composition and surface properties, this work analyzes its catalytic performance under both normal and aging conditions, confirming that peroxide and superoxide dismutase (SOD) activity are crucial for its anti-aging therapeutic function. Subsequently, the chiral-dependent therapeutic effect is validated and the senolytic performance of D-handed PtPd2CuFe across several aging models is confirmed. Through multi-Omics analyses, this work explores the mechanism underlying the senolytic action exerted by nanozyme in depth. It is confirm that exposure to senescent conditions leads to the enrichment of copper and iron atoms in their lower oxidation states, disrupting the iron-thiol cluster in mitochondria and lipoic acid transferase, as well as oxidizing unsaturated fatty acids, triggering a cascade of cuproptosis and ferroptosis. Additionally, the concentration-dependent anti-aging effects of nanozyme is validated. Even an ultralow dose, the therapeutic can still act as a senomorphic, reducing the effects of senescence. Given its broad-spectrum action and concentration-adjustable anti-aging potential, this work confirms the remarkable therapeutic capability of D-handed PtPd2CuFe in managing atherosclerosis, a disease involving various types of senescent cells.


Subject(s)
Atherosclerosis , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Humans , Animals , Mice , Copper/chemistry , Copper/pharmacology , Alloys/chemistry , Alloys/pharmacology , Iron/chemistry , Superoxide Dismutase/metabolism , Cellular Senescence/drug effects , Ferroptosis/drug effects
15.
ACS Appl Mater Interfaces ; 16(19): 24274-24294, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38699930

ABSTRACT

In the field of bone tissue engineering, recently developed Zn alloy scaffolds are considered potential candidates for biodegradable implants for bone regeneration and defect reconstruction. However, the clinical success of these alloys is limited due to their insufficient surface bioactivities. Further, the higher concentration of Zn2+ produced during degradation promotes antibacterial activity, but deteriorates osteogenic properties. This study fabricated an Azadirachta indica (neem)-assisted brushite-hydroxyapatite (HAp) coating on the recently developed Zn-2Cu-0.5Mg alloy to tackle the above dilemma. The microstructure, degradation behavior, antibacterial activity, and hemocompatibility, along with in vitro and in vivo cytocompatibility of the coated alloys, are systematically investigated. Microstructural analysis reveals flower-like morphology with uniformly grown flakes for neem-assisted deposition. The neem-assisted deposition significantly improves the adhesion strength from 12.7 to 18.8 MPa, enhancing the mechanical integrity. The potentiodynamic polarization study shows that the neem-assisted deposition decreases the degradation rate, with the lowest degradation rate of 0.027 mm/yr for the ZHN2 sample. In addition, the biomineralization process shows the apatite formation on the deposited coating after 21 days of immersion. In vitro cytotoxicity assay exhibits the maximum cell viability of 117% for neem-assisted coated alloy in 30% extract after 5d and the improved cytocompatibility which is due to the controlled release of Zn2+ ions. Meanwhile, neem-assisted coated alloy increases the ZOI by 32 and 24% for Gram-positive and Gram-negative bacteria, respectively. Acceptable hemolysis (<5%) and anticoagulation parameters demonstrate a promising hemocompatibility of the coated alloy. In vivo implantation illustrates a slight inflammatory response and vascularization after 2 weeks of subcutaneous implantation, and neo-bone formation in the defect areas of the rat femur. Micro-CT and histology studies demonstrate better osseointegration with satisfactory biosafety response for the neem-assisted coated alloy as compared to that without neem-assisted deposition. Hence, this neem-assisted brushite-Hap coating strategy elucidates a new perspective on the surface modification of biodegradable implants for the treatment of bone defects.


Subject(s)
Alloys , Calcium Phosphates , Coated Materials, Biocompatible , Zinc , Alloys/chemistry , Alloys/pharmacology , Zinc/chemistry , Zinc/pharmacology , Animals , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Humans , Durapatite/chemistry , Durapatite/pharmacology , Materials Testing , Mice , Green Chemistry Technology , Absorbable Implants
16.
ACS Appl Mater Interfaces ; 16(19): 24321-24340, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38700914

ABSTRACT

In current clinical practices related to orthopedics, dental, and cardiovascular surgeries, a number of biomaterial coatings, such as hydroxyapatite (HAp), diamond-like carbon (DLC), have been used in combination with metallic substrates (stainless steel, Ti6Al4V alloy, etc.). Although SiBCN coatings are widely explored in material science for diverse applications, their potential remains largely unexplored for biomedical applications. With this motivation, the present work reports the development of SiBxCyNzOm coatings on a Ti6Al4V substrate, employing a reactive radiofrequency (RF) magnetron sputtering technique. Three different coating compositions (Si0.27B0.10C0.31N0.07O0.24, Si0.23B0.06C0.21N0.22O0.27, and Si0.20B0.05C0.19N0.20O0.35) were obtained using a Si2BC2N target and varying nitrogen flow rates. The hydrophilic properties of the as-synthesized coatings were rationalized in terms of an increase in the number of oxygen-containing functional groups (OH and NO) on the surface, as probed using XPS and FTIR analyses. Furthermore, the cellular monoculture of SVEC4-10 endothelial cells and L929 fibroblasts established good cytocompatibility. More importantly, the coculture system of SVEC4-10 and L929, in the absence of growth factors, demonstrated clear cellular phenotypical changes, with extensive sprouting leading to tube-like morphologies on the coating surfaces, when stimulated using a customized cell stimulator (StimuCell) with 1.15 V/cm direct current (DC) electric field strength for 1 h. In addition, the hemocompatibility assessment using human blood samples revealed clinically acceptable hemolysis, less erythrocyte adhesion, shorter plasma recalcification, and reduced risk for thrombosis on the SiBxCyNzOm coatings, when compared to uncoated Ti6Al4V. Taken together, the present study unambiguously establishes excellent cytocompatibility, hemocompatibility, and defines the preangiogenic properties of SiBxCyNzOm bioceramic coatings for potential biomedical applications.


Subject(s)
Alloys , Coated Materials, Biocompatible , Materials Testing , Titanium , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Alloys/chemistry , Alloys/pharmacology , Titanium/chemistry , Titanium/pharmacology , Humans , Animals , Mice , Endothelial Cells/drug effects , Endothelial Cells/cytology , Cell Line , Surface Properties , Fibroblasts/drug effects , Fibroblasts/cytology , Neovascularization, Physiologic/drug effects
17.
Biomater Adv ; 161: 213882, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38710121

ABSTRACT

Metallic lattice scaffolds are designed to mimic the architecture and mechanical properties of bone tissue and their surface compatibility is of primary importance. This study presents a novel surface modification protocol for metallic lattice scaffolds printed from a superelastic Ti-Zr-Nb alloy. This protocol consists of dynamic chemical etching (DCE) followed by silver nanoparticles (AgNP) decoration. DCE, using an 1HF + 3HNO3 + 12H2O23% based solution, was used to remove partially-fused particles from the surfaces of different as-built lattice structures (rhombic dodecahedron, sheet gyroid, and Voronoi polyhedra). Subsequently, an antibacterial coating was synthesized on the surface of the scaffolds by a controlled (20 min at a fixed volume flowrate of 500 mL/min) pumping of the functionalization solutions (NaBH4 (2 mg/mL) and AgNO3 (1 mg/mL)) through the porous structures. Following these treatments, the scaffolds' surfaces were found to be densely populated with Ag nanoparticles and their agglomerates, and manifested an excellent antibacterial effect (Ag ion release rate of 4-8 ppm) suppressing the growth of both E. coli and B. subtilis bacteria up to 99 %. The scaffold extracts showed no cytotoxicity and did not affect cell proliferation, indicating their safety for subsequent use as implants. A cytocompatibility assessment using MG-63 spheroids demonstrated good attachment, spreading, and active migration of cells on the scaffold surface (over 96 % of living cells), confirming their biotolerance. These findings suggest the promise of this surface modification approach for developing superelastic Ti-Zr-Nb scaffolds with superior antibacterial properties and biocompatibility, making them highly suitable for bone implant applications.


Subject(s)
Anti-Bacterial Agents , Metal Nanoparticles , Silver , Surface Properties , Tissue Scaffolds , Titanium , Zirconium , Silver/chemistry , Silver/pharmacology , Metal Nanoparticles/chemistry , Titanium/chemistry , Titanium/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Tissue Scaffolds/chemistry , Zirconium/chemistry , Zirconium/pharmacology , Humans , Niobium/chemistry , Niobium/pharmacology , Lasers , Escherichia coli/drug effects , Alloys/chemistry , Alloys/pharmacology , Bacillus subtilis/drug effects , Powders , Materials Testing , Cell Proliferation/drug effects
18.
Acta Biomater ; 180: 183-196, 2024 05.
Article in English | MEDLINE | ID: mdl-38604465

ABSTRACT

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.


Subject(s)
Absorbable Implants , Coated Materials, Biocompatible , Magnesium , Nanocomposites , Stents , Animals , Rabbits , Magnesium/chemistry , Magnesium/pharmacology , Nanocomposites/chemistry , Corrosion , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Biofouling/prevention & control , Dioxanes/chemistry , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Polymers/chemistry , Polymers/pharmacology , Alloys/chemistry , Alloys/pharmacology
19.
ACS Appl Bio Mater ; 7(5): 2762-2780, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38629138

ABSTRACT

In the present study, we have discussed the influence of forging temperature (623 K (FT623), 723 K (FT723) and 823 K (FT823)) on microstructure and texture evolution and its implication on mechanical behavior, in vitro-in vivo biocorrosion, antibacterial response, and cytocompatibility of microalloyed Mg-Zr-Sr-Ce alloy. Phase analysis, SEM, and TEM characterization confirm the presence of Mg12Ce precipitate, and its stability was further validated by performing ab initio molecular dynamic simulation study. FT723 exhibits strengthened basal texture, higher fraction of second phases, and particle-stimulated nucleation-assisted DRX grains compared to other two specimens, resulting in superior strength with comparable ductility. FT723 also exhibits superior corrosion resistance mainly due to the strengthened basal texture and lower dislocation density. All the specimens exhibit excellent antibacterial behavior with Gram-negative E. coli, Gram-positive Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. 100% reduction of bacterial growth is observed within 24 h of culture of the specimens. Cytocompatibility was determined by challenging specimen extracts with the MC3T3-E1 cell lines. FT723 specimen exhibits the highest cell proliferation and alkaline phosphatase activity (ALP) because of its superior corrosion resistance. The ability of the specimens to be used in orthopedic implant application was evaluated by in vivo study in rabbit femur. Neither tissue-related infection nor the detrimental effect surrounding the implant was confirmed from histological analysis. Significant higher bone regeneration surrounding the FT723 specimen was observed in SEM analysis and fluorochrome labeling. After 60 days, the FT723 specimen exhibits the highest bone formation, suggesting it is a suitable candidate for orthopedic implant application.


Subject(s)
Alloys , Anti-Bacterial Agents , Biocompatible Materials , Materials Testing , Osteogenesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Alloys/chemistry , Alloys/pharmacology , Osteogenesis/drug effects , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Mice , Zirconium/chemistry , Zirconium/pharmacology , Microbial Sensitivity Tests , Particle Size , Cell Differentiation/drug effects , Rabbits , Magnesium/chemistry , Magnesium/pharmacology , Escherichia coli/drug effects , Pseudomonas aeruginosa/drug effects , Cell Proliferation/drug effects , Strontium/chemistry , Strontium/pharmacology , Molecular Dynamics Simulation , Cell Line , Temperature
20.
Colloids Surf B Biointerfaces ; 238: 113880, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38581836

ABSTRACT

In the field of orthopedics, it's crucial to effectively slow down the degradation rate of Mg alloys. This study aims to improve the degradation behavior of Mg-Zn-Ca alloys by electrodepositing fluorohydroxyapatite (FHA). We investigated the microstructure and bond strength of the deposition, as well as degradation and cellular reactions. After 15-30 days of degradation in Hanks solution, FHA deposited alloys showed enhanced stability and less pH change. The strong interfacial bond between FHA and the Mg-Zn-Ca substrate was verified through scratch tests (Critical loads: 10.73 ± 0.014 N in Mg-Zn-0.5Ca alloys). Cellular studies demonstrated that FHA-coated alloys exhibited good cytocompatibility and promoted the growth of MC3T3-E1 cells. Further tests showed FHA-coated alloys owed improved early bone mineralization and osteogenic properties, especially in Mg-Zn-0.5Ca. This research highlighted the potential of FHA-coated Mg-Zn-0.5Ca alloys in orthopedics applications.


Subject(s)
Alloys , Calcium , Magnesium , Zinc , Alloys/chemistry , Alloys/pharmacology , Corrosion , Animals , Zinc/chemistry , Zinc/pharmacology , Magnesium/chemistry , Mice , Calcium/chemistry , Calcium/metabolism , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Surface Properties , Materials Testing , Cell Proliferation/drug effects , Hydroxyapatites/chemistry , Cell Line , Durapatite/chemistry , Durapatite/pharmacology
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